HP1c regulates development and gut homeostasis by suppressing Notch signaling through Su(H).

Notch signaling and epigenetic factors are known to play critical roles in regulating tissue homeostasis in most multicellular organisms, but how Notch signaling coordinates with epigenetic modulators to control differentiation remains poorly understood. Here, we identify heterochromatin protein 1c (HP1c) as an essential epigenetic regulator of gut homeostasis in Drosophila. Specifically, we observe that HP1c loss-of-function phenotypes resemble those observed after Notch signaling perturbation and that HP1c interacts genetically with components of the Notch pathway.

Fecal Fungal Dysbiosis in Chinese Patients With Alzheimer's Disease.

Gut bacterial dysbiosis plays a vital role in the development of Alzheimer's disease (AD). However, our understanding of alterations to the gut fungal microbiota and their correlations with host immunity in AD is still limited. Samples were obtained from 88 Chinese patients with AD, and 65 age- and gender-matched, cognitively normal controls.

TCM network pharmacology: A new trend towards combining computational, experimental and clinical approaches.

Traditional Chinese medicine (TCM) is a precious treasure of the Chinese nation and has unique advantages in the prevention and treatment of diseases. The holistic view of TCM coincides with the new generation of medical research paradigm characterized by network and system. TCM gave birth to a new method featuring holistic and systematic "network target", a core theory and method of network pharmacology.

Root Endophytic Fungal Community and Carbon and Nitrogen Stable Isotope Patterns Differ among Species (Orchidaceae).

Orchids of the genus are well-known ornamental plants and sources of traditional medicine in Asia that rely on the symbiotic relationship with root endophytic fungi throughout their whole life cycle. However, little is known about their fungal partners, infection pattern, and pathways of carbon gain. We investigated carbon and nitrogen stable isotope patterns in different organs of three species, identified the root endophytic fungal community composition, and determined mycorrhizal colonization rates.

Advancements in stem cell-derived hepatocyte-like cell models for hepatotoxicity testing.

Drug-induced liver injury (DILI) is one of the leading causes of clinical trial failures and high drug attrition rates. Currently, the commonly used hepatocyte models include primary human hepatocytes (PHHs), animal models, and hepatic cell lines. However, these models have disadvantages that include species-specific differences or inconvenient cell extraction methods.

Genome-wide association study on Northern Chinese identifies KLF2, DOT1L and STAB2 associated with systemic lupus erythematosus.

Objectives: To identify novel genetic loci associated with systemic lupus erythematosus (SLE) and to evaluate potential genetic differences between ethnic Chinese and European populations in SLE susceptibility.

Methods: A new genome-wide association study (GWAS) was conducted from Jining, North China, on 1506 individuals (512 SLE cases and 994 matched healthy controls). The association results were meta-analysed with existing data on Chinese populations from Hong Kong, Guangzhou and Central China, as well as GWAS results from four cohorts of European ancestry.

Fecal Fungi Dysbiosis in Nonalcoholic Fatty Liver Disease.

Objective: Nonalcoholic fatty liver disease (NAFLD) can systematically harm more aspects of human health than just the liver. In addition to the potential roles of the gut microbiota in NAFLD, commensal fungi can functionally replace intestinal bacteria in maintaining the host immune response in the gut by reversing disease susceptibility. Therefore, gut commensal fungi should be studied to help understand NAFLD.

Design, synthesis and biological evaluation of novel benzoxaborole derivatives as potent PDE4 inhibitors for topical treatment of atopic dermatitis.

In this work, a series of structurally novel benzoxaborole derivatives were designed, synthesized and biologically evaluated as PDE4 inhibitors for battling atopic dermatitis (AD). Among them, the majority exhibited superior PDE4B inhibitory activities to that of the lead compound Crisaborole, an approved PDE4 inhibitor. In particular, 72, the most potent PDE4B inhibitor throughout this series, displayed 136-fold improved enzymatic activity (IC = 0.

Molecular Entrapment of Polymers by Pyrogallol[4]arenes.

Macromolecular recognition systems are difficult to construct because extremely high recognition ability is required to form a stable host-guest complex toward macromolecules. Herein, we report a novel host-guest recognition motif based on C-propylpyrogallol[4]arene () and a commercially available polymer, polyethylene glycol (PEG). The results show that can selectively entrap PEG with higher molecular weights to form bilayered host-guest complex structures.

Self-Assembly of a Semiconductive and Photoactive Heterobimetallic Metal-Organic Capsule.

We report the synthesis of a novel metal-organic capsule constructed from six pyrogallol[4]arene macrocycles, which are switched together by 16 Fe and 16 Co ions. This supramolecular structure is the first instance of a spheroidal heterometallic nanocage assembled through a one-step metal-ligand coordination approach. This new assembly also demonstrates an important proof of concept through the formation of multiple heterometallic metal-metal interactions within the capsule framework.

Alterations of the Fecal Microbiota in Chinese Patients With Multiple Sclerosis.

Mounting evidence indicates that alterations in the intestinal microbiota may be associated with neurological disorders such as multiple sclerosis (MS). MS is a putative autoimmune disease of the central nervous system. However, it has not been determined whether the intestinal microbiota and host immune status are altered in Chinese patients with stable MS.

Global, Regional, and National Burden of Chronic Myeloid Leukemia, 1990-2017: A Systematic Analysis for the Global Burden of Disease Study 2017.

Background: With the advent of tyrosine kinase inhibitors (TKIs), the prognosis of chronic myeloid leukemia (CML) seems to have dramatically improved over the last two decades. Accurate information of the global burden of CML is critical for direct health policy and healthcare resource allocation in the era of high-cost TKI therapy.

Objective: This study aimed to evaluate the health burden of CML at global, regional, and national levels from 1990 to 2017.

Temporal Variation in Community Composition of Root Associated Endophytic Fungi and Carbon and Nitrogen Stable Isotope Abundance in Two Species (Orchidaceae).

Mycorrhizae are an important energy source for orchids that may replace or supplement photosynthesis. Most mature orchids rely on mycorrhizae throughout their life cycles. However, little is known about temporal variation in root endophytic fungal diversity and their trophic functions throughout whole growth periods of the orchids.

Structure-Based Drug Design and Synthesis of PI3Kα-Selective Inhibitor (PF-06843195).

The phosphoinositide 3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway is a frequently dysregulated pathway in human cancer, and PI3Kα is one of the most frequently mutated kinases in human cancer. A PI3Kα-selective inhibitor may provide the opportunity to spare patients the side effects associated with broader inhibition of the class I PI3K family. Here, we describe our efforts to discover a PI3Kα-selective inhibitor by applying structure-based drug design (SBDD) and computational analysis.

Two-dimensional GaO monolayer with tunable band gap and high hole mobility.

By means of density functional theory and unbiased structure search computations, we systematically investigated the stability and electronic properties of a new Ga2O2 monolayer. The phonon spectra and ab initio molecular dynamics simulations show that the Ga2O2 monolayer is dynamically and thermally stable. Moreover, it also shows superior open-air stability.

A novel three-TMH Na/H antiporter and the functional role of its oligomerization.

Na/Hantiportersare a category of ubiquitous transmembrane proteins with various important physiological roles in almost all living organisms ranging from bacteria to humans. However, the knowledge of novel Na/Hantiporters remains to be broadened, and the functional roles ofoligomerization in theseantiportershave not yet been thoroughly understood. Here, we reported functional analysis of an unknown transmembrane protein composed of 103 amino acid residues.

Supramolecular Tessellations via Pillar[]arenes-Based Exo-Wall Interactions.

Supramolecular tessellation is a newly emerging and promising area in supramolecular chemistry because of its unique structural aesthetics and potential applications. Herein, we investigate the "exo-wall" interactions of pillar[]arenes and prepare fantastic hexagonal supramolecular tessellations based on perethylated pillar[6]arenes () with electron-deficient molecules 1,5-difluoro-2,4-dinitrobenzene () and tetrafluoro-1,4-benzoquinone (). The crystal structures clearly confirm that can form highly ordered hexagonal 2D tiling patterns with / as linkers through cocrystallization.

Treatment with can suppress Aβ accumulation and neuroinflammation in APP/PS1 mice.

Background: Alzheimer's disease (AD), being a complex disorder, is affected either by genetic or environmental factors or both. It is observed that there is an excessive accumulation of amyloid β (Aβ) in the extracellular space of the brain. AD is the first neurodegenerative disease in the elderly, and so far there is no effective treatment.

Acid/Base-Tunable Unimolecular Chirality Switching of a Pillar[5]azacrown [1]Catenane.

Stimuli-responsive unimolecular chirality switching is a highly intriguing topic because the molecular structure as well as its function can be adjusted simultaneously by a switching process. Herein, a novel acid/base-tunable unimolecular chirality switching system based on a pillar[5]azacrown [1]catenane is reported. The bicyclic pillar[5]azacrown [1]catenane is synthesized through fusing an azacrown ring onto one repeating unit of a pillar[5]arene.

Steroid receptor coactivator-1 enhances the stemness of glioblastoma by activating long noncoding RNA XIST/miR-152/KLF4 pathway.

Glioblastoma (GBM) recurrence is attributed to the presence of therapy-resistant glioblastoma stem cells. Steroid receptor coactivator-1 (SRC-1) acts as an oncogenic regulator in many human tumors. The relationship between SRC-1 and GBM has not yet been studied.

The Toxicology Investigators Consortium Case Registry-the 2019 Annual Report.

The Toxicology Investigators Consortium (ToxIC) Registry was established by the American College of Medical Toxicology (ACMT) in 2010. The Registry collects data from participating sites with the agreement that all bedside medical toxicology consultation will be entered. This tenth annual report summarizes the Registry's 2019 data and activity with its additional 7177 cases.

Pillar[5]arene-Based Solid-State Supramolecular Polymers with Suppressed Aggregation-Caused Quenching Effects and Two-Photon Excited Emission.

Herein we develop a new pillar[5]arene-mediated supramolecular polymerization strategy to control the assembly of dyes 4,7-di-2-thienyl-2,1,3-benzothiadiazole and 4,7-di-2-thienyl-2,1,3-benzoselenadiazole in the solid state. The resulting supramolecular polymeric structures drive the dye aggregates in the solid state from parallel alignments to highly ordered "head-to-tail" structures, which effectively suppresses excimer formation and thus aggregation-caused quenching effects and enhances the solid-state emission efficiency by almost 1 order of magnitude. This, together with two-photon excited emission, endows these solid-state polymers with exciting potential in optoelectronic, photonic, and bioimaging applications.

Network Pharmacology to Uncover the Biological Basis of Spleen Qi Deficiency Syndrome and Herbal Treatment.

Spleen qi deficiency (SQD) syndrome is one of the basic traditional Chinese medicine (TCM) syndromes related to various diseases including chronic inflammation and hypertension and guides the use of many herbal formulae. However, the biological basis of SQD syndrome has not been clearly elucidated due to the lack of appropriate methodologies. Here, we propose a network pharmacology strategy integrating computational, clinical, and experimental investigation to study the biological basis of SQD syndrome.

A novel three-dimensional tetranuclear Co coordination polymer with water hexamers based on the V-shaped tetracarboxylate ligand 4-(2,4-dicarboxylatophenoxy)phthalate.

A new coordination polymer (CP), namely, poly[[diaquatris[μ-1,4-bis(1H-imidazol-1-yl)benzene]bis[μ-4-(2,4-dicarboxylatophenoxy)phthalato]tetracobalt(II)] hexahydrate], {[Co(CHO)(CHN)(HO)]·6HO}, has been synthesized by solvothermal reaction. The CP was fully characterized by IR spectroscopy, elemental analysis, thermogravimetric analysis, and powder and single-crystal X-ray diffraction. It presents a three-dimensional (3D) structure based on tetranuclear Co secondary building units (SBUs) with a tfz-d net and point symbol (4)(4·6·8).